Purpose To assess subspecialty practice characteristics of the U.S. radiologist workforce. Materials and Methods This study used the Medicare Physician and Other Supplier Public Use File and did not constitute human subject research. The authors identified 33 090 radiologists who billed for professional services between 2012 and 2014 and used a validated classification system to map services to seven subspecialties and quantify subspecialty-focused effort on the basis of work relative value units (RVUs). Radiologists with more than half of their billed work RVUs in a single subspecialty were designated subspecialists; the remainder were classified as generalists. Matching radiologists with various characteristics extracted from other publicly available data sets, associations were explored through use of analysis of variance and multivariable logistic regression. Results More than half (55.3%) of U.S. radiologists practice predominantly as generalists but dedicate on average 36.0% effort to one subspecialty. Among radiologists practicing as majority subspecialists, neuroradiologists (10.1% of all radiologists) and breast imagers (8.4%) are most common. Subspecialization is more common (P < .001) among radiologists who are female, are earlier in their career, work in larger practices, have academic affiliations, and practice in the Northeast. By subspecialty, female representation varies from 8.6% (interventional radiology) to 63.1% (breast imaging); cardiothoracic imagers were more commonly early career radiologists, and nuclear medicine physicians were later career radiologists. Subspecialization is considerably more common in larger (≥100 members) practices (63.1%). An academic affiliation is the strongest independent predictor of subspecialization (odds ratio, 3.56; 95% confidence interval: 3.30, 3.84). Conclusion Despite an increased focus on radiology subspecialization, most U.S. radiologists are majority general radiologists on the basis of their work RVUs. Subspecialization is by far more prevalent in larger and academic practices. © RSNA, 2017 Online supplemental material is available for this article.